Clinical Information

Bleeding problems may be associated with a wide variety of coagulation abnormalities or may be due to problems not associated with coagulation (trauma and surgery as obvious examples). A partial listing of causes follows.

-Deficiency or functional abnormality (congenital or acquired) of any of the following coagulation proteins: fibrinogen (factor I), factor II (prothrombin), factor V, factor VII, factor VIII (hemophilia A), factor IX (hemophilia B), factor X, factor XI (hemophilia C; bleeding severity not  always proportionate to factor level), factor XIII (fibrin-stabilizing factor), von Willebrand factor (VWF antigen and activity), and alpha-2 plasmin inhibitor and plasminogen activator inhibitor (PAI-I; severe deficiency in rare cases). Neither alpha-2 plasmin inhibitor nor PAI-I are included as a routine bleeding diathesis assay component, but either can be performed if indicated or requested.

-Deficiency (thrombocytopenia) or functional abnormality of platelets such as congenital (eg, Glanzmann thrombasthenia, Bernard-Soulier syndrome, storage pool disorders) and acquired (eg, myeloproliferative disorders, uremia, drugs) disorders. Platelet function abnormalities cannot be studied on mailed-in specimens.

-Specific factor inhibitors (most commonly directed against factor VIII); factor inhibitors occur in 10% to15% of the hemophilia population and are more commonly associated with severe deficiencies of factor VIII or IX (antigen <1%). The inhibitor appears in response to transfusion therapy with factor concentrates with no correlation of occurrence and amount of therapy. Factor VIII inhibitors may occur spontaneously in the postpartum patient, with certain malignancies, in association with autoimmune disorders (eg, rheumatoid arthritis, systemic lupus erythematosus), in the elderly, and for no apparent reason.

-Other acquired causes of increased bleeding include paraproteinemia; other factor-specific inhibitors, including those against factor V, factor XI; or virtually any of the coagulation proteins.

-Acute disseminated intravascular coagulation/intravascular coagulation and fibrinolysis (DIC/ICF), which is a fairly common cause of bleeding. Bleeding can also occur in patients with chronic ICF.